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Infection and Immunity, March 2001, p. 1739-1746, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1739-1746.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Coiling Phagocytosis of Borrelia burgdorferi by Primary Human Macrophages Is Controlled by CDC42Hs and Rac1 and Involves Recruitment of Wiskott-Aldrich Syndrome Protein and Arp2/3 Complex

Stefan Linder,1 Christiane Heimerl,2 Volker Fingerle,2 Martin Aepfelbacher,2 and Bettina Wilske2,*

Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten,1 and Max von Pettenkofer-Institut für Medizinische Mikrobiologie,2 Ludwig-Maximilians-Universität, 80336 Munich, Germany

Received 29 September 2000/Returned for modification 11 November 2000/Accepted 30 November 2000

Lyme borreliosis is a multisystemic disorder primarily affecting the skin, nervous system, and joints. It is caused by the spirochete Borrelia burgdorferi sensu lato and is transmitted via ticks of the Ixodidae family. Persistence of borreliae within macrophages has been implicated in the often chronic history of borreliosis. The uptake of B. burgdorferi by professional phagocytes occurs predominantly by coiling phagocytosis, a host cell-driven process in which single pseudopods wrap around and engulf the spirochetes. In the present study, we investigated the molecular machinery and the signal transduction pathways controlling the formation of these unique uptake structures. We found that the phagocytosis of borreliae by primary human macrophages is accompanied by the formation of f-actin-rich structures, which in their morphological organization correspond well to the earlier described coiling pseudopods. Further experiments revealed that Wiskott-Aldrich Syndrome protein and Arp2/3 complex, major regulators of actin polymerization, are also recruited to these sites of actin accumulation. In addition, inhibition of an upstream regulator of Wiskott-Aldrich Syndrome protein, the Rho-family GTPase CDC42Hs, greatly inhibited the occurrence of borrelia-induced phagocytic uptake structures. Inhibition of Rac1, another Rho family GTPase, had a less-pronounced inhibitory effect, while blocking of Rho activity showed no discernible influence. These results suggest that basic mechanisms of actin polymerization that control other types of phagocytosis are also functional in the formation of the morphologically unique uptake structures in coiling phagocytosis. Our findings should enhance the understanding of the infection process of B. burgdorferi and contribute to devising new strategies for countering Lyme disease.

* Corresponding author. Mailing address: Max von Pettenkofer-Institut, Ludwig-Maximilians-Universität, Pettenkoferstr. 9a, 80336 Munich, Germany. Phone: 49-89-5160-5231. Fax: 49-89-5160-4757. E-mail: Bettina.Wilske{at}mvp-bak.med.uni-muenchen.de.

Infection and Immunity, March 2001, p. 1739-1746, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1739-1746.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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